Introduction: Left atrial size is an important predictor of adverse cardiovascular outcomes. Systemic inflammation leads to cardiac dysfunction and predicts adverse cardiovascular events, but the association between inflammation and left atrial size in young adults free of overt cardiovascular disease is not known.Hypothesis: We investigated the hypothesis that a higher C-reactive protein (CRP) level, a marker of inflammation, is independently associated with larger left atrial size.Methods: The Coronary Artery Risk Development in Young Adults (CARDIA) study is a prospective cohort study that enrolled 5115 asymptomatic black and white participants ages 18-30. At Year 5, all available participants underwent a study echocardiogram that was repeated in a third of participants at the Year 10 examination. At Year 7, all available participants underwent high sensitivity CRP testing. We used multivariable linear regression to investigate the association between CRP and height-indexed left atrial dimension (LADI). We also evaluated whether the association between CRP and LADI differed by race, sex, and body mass index (BMI) using interaction terms.Results: Among the 1464 participants with CRP data from Year 7 and echocardiographic data from Year 10 (age 28-40 years), the median CRP was 1.1 mg/L (IQR 0.5 - 3.2) and the mean LADI was 2.13 ± 0.27 cm/m. We found a statistically significant association of CRP with LADI; (β = 0.21 cm/m, p < 0.001); this association did not vary by age, sex, and race, but did vary by BMI (p for interaction 30 kg/m2), each standard deviation increase in log-CRP was associated with a 0.08 cm/m increase in LADI in models adjusted for age, sex, and race (p < 0.001); there was no association between CRP and LADI in non-obese CARDIA participants. Among the obese participants, those in the highest quartile of CRP (> 3.2 mg/L) had a 0.21 cm/m larger LADI compared to those in the lowest quartile (p = 0.01). The association was unchanged after adjusting for diabetes, hypertension, smoking, physical activity, family history of coronary disease, heart rate, lipids, glucose, insulin, echo parameters, and even remained after additional adjustment for BMI among the obese. We observed the same findings among the larger cohort of 3919 participants with echocardiograms at the Year 5 examination, (β = 0.12 cm/m, p = 0.006 among obese participants).Conclusions: Elevated levels of CRP are associated with larger left atrial size in obese young adults, but not in the non-obese, suggesting a link between inflammation and left atrial size even in early, young adulthood. Whether chronic low-grade systemic inflammation is an early cause of subclinical cardiac dysfunction in obese individuals, or merely a marker of a disease process initiated by obesity, requires further study.